Citation: Jie Fan, Xinqian Lv, Saixia Yang, Shuxian Geng, Jifei Yang, Yaru Zhao, Zhonghui Zhang, Zhijie Liu, Guiquan Guan, Jianxun Luo, Qiaoying Zeng, Hong Yin, Qingli Niu. OGG1 inhibition suppresses African swine fever virus replication .VIROLOGICA SINICA, 2023, 38(1) : 96-107.  http://dx.doi.org/10.1016/j.virs.2022.11.006

OGG1 inhibition suppresses African swine fever virus replication

  • Corresponding author: Qiaoying Zeng, zengqy@gsau.edu.cn
    Qingli Niu, niuqingli@caas.cn
  • Received Date: 21 June 2022
    Accepted Date: 18 November 2022
    Available online: 23 November 2022
  • African swine fever virus (ASFV) is an important pathogen that causes a highly contagious and lethal disease in swine, for which neither a vaccine nor treatment is available. The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises the oxidative base lesion 8-oxo-7,8-dihydroguanine (8-oxoG), has been linked to the pathogenesis of different diseases associated with viral infections. However, the role of OGG1-base excision repair (BER) in ASFV infection has been poorly investigated. Our study aimed to characterize the alteration of host reactive oxygen species (ROS) and OGG1 and to analyse the role of OGG1 in ASFV infection. We found that ASFV infection induced high levels and dynamic changes in ROS and 8-oxoG and consistently increased the expression of OGG1. Viral yield, transcription level, and protein synthesis were reduced in ASFV-infected primary alveolar macrophages (PAMs) treated by TH5487 or SU0268 inhibiting OGG1. The expression of BER pathway associated proteins of ASFV was also suppressed in OGG1-inhibited PAMs. Furthermore, OGG1 was found to negatively regulate interferon β (IFN-β) production during ASFV infection and IFN-β could be activated by OGG1 inhibition with TH5487 and SU0268, which blocked OGG1 binding to 8-oxoG. Additionally, the interaction of OGG1 with viral MGF360-14-L protein could disturb IFN-β production to further affect ASFV replication. These results suggest that OGG1 plays the crucial role in successful viral infection and OGG1 inhibitors SU0268 or TH5487 could be used as antiviral agents for ASFV infection.

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    OGG1 inhibition suppresses African swine fever virus replication

      Corresponding author: Qiaoying Zeng, zengqy@gsau.edu.cn
      Corresponding author: Qingli Niu, niuqingli@caas.cn
    • a. College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China;
    • b. African Swine Fever Regional Laboratory of China (Lanzhou), State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China;
    • c. Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou University, Yangzhou, 225009, China

    Abstract: African swine fever virus (ASFV) is an important pathogen that causes a highly contagious and lethal disease in swine, for which neither a vaccine nor treatment is available. The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises the oxidative base lesion 8-oxo-7,8-dihydroguanine (8-oxoG), has been linked to the pathogenesis of different diseases associated with viral infections. However, the role of OGG1-base excision repair (BER) in ASFV infection has been poorly investigated. Our study aimed to characterize the alteration of host reactive oxygen species (ROS) and OGG1 and to analyse the role of OGG1 in ASFV infection. We found that ASFV infection induced high levels and dynamic changes in ROS and 8-oxoG and consistently increased the expression of OGG1. Viral yield, transcription level, and protein synthesis were reduced in ASFV-infected primary alveolar macrophages (PAMs) treated by TH5487 or SU0268 inhibiting OGG1. The expression of BER pathway associated proteins of ASFV was also suppressed in OGG1-inhibited PAMs. Furthermore, OGG1 was found to negatively regulate interferon β (IFN-β) production during ASFV infection and IFN-β could be activated by OGG1 inhibition with TH5487 and SU0268, which blocked OGG1 binding to 8-oxoG. Additionally, the interaction of OGG1 with viral MGF360-14-L protein could disturb IFN-β production to further affect ASFV replication. These results suggest that OGG1 plays the crucial role in successful viral infection and OGG1 inhibitors SU0268 or TH5487 could be used as antiviral agents for ASFV infection.

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